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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Interconversions of haloperidol and reduced haloperidol in guinea pig and rat liver microsomes.

An alcohol metabolite of haloperidol, reduced haloperidol, is present in the tissues of haloperidol-treated patients. We have studied whether rat and guinea pig liver microsomes have the capability to reduce haloperidol and thus serve as models for human haloperidol metabolism. Interestingly, the rat microsomes did not reduce haloperidol, but possessed an NADPH-dependent, carbon monoxide-inhibited mechanism to oxidize the reduced haloperidol back to haloperidol. Guinea pig microsomes efficiently reduced haloperidol molecules in a fashion not dependent on nicotinamide cofactors and not inhibited by carbon monoxide. Both of these activities were confined to the microsomal fraction. In guinea pigs, reduction of haloperidol was observed also in kidney slices, whereas brain slices proved inactive. Reduced haloperidol was also oxidized to haloperidol to a small extent in guinea pig microsomes. These in vitro experiments confirm our findings in vivo, which showed that in rats haloperidol is not reduced, while guinea pigs have a very active mechanism for reducing haloperidol. Thus, guinea pigs constitute a model for human haloperidol metabolism, and they should be used for further characterization of the reductive drug-metabolizing system.[1]


  1. Interconversions of haloperidol and reduced haloperidol in guinea pig and rat liver microsomes. Korpi, E.R., Costakos, D.T., Wyatt, R.J. Biochem. Pharmacol. (1985) [Pubmed]
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